Research conducted in this laboratory has shown that high androgen responder (HAR) mice produce low immune responses to a wide spectrum of antigens. The current proposal aims to understand the mechanisms underlying the low immune responses of HAR mice and the biological implications of these low responses in terms of health and host survival. The long term goals of the research are to gain a greater understanding of host variability in the immune response by exploring the role of high androgen responsiveness as a non specific modulator of immune function. The specific aims of this proposal are: I. To determine whether the low immune responses of HAR mice are related to deficiencies or imbalances in subsets of splenic B cells, NK cells or thymus suppressor cells; II. To determine whether the low immune responses of HAR mice can be overcome using protein conjugates of polysaccharide antigens or transplanted spleens; III. To determine whether the low antibody responses of HAR mice to soluble pneumococcal polysaccharides jeopardizes them in terms of health and survival when challenged by live organisms; IV. To study the genetic transmission of high androgen responsiveness and low immune function in reciprocal crosses between HAR and low androgen responder strains; and V. to investigate the role of androgens on the developing lymphomyeloid system by using neonatal treatment with anti-androgens. The procedures to be used include flow cytometric analyses of spleen and thymus subsets, 51Cr assays of NK cells, radioimmunoassays, ELISAs, transplantation, mitogenic and enzyme assays. MBRS students will have the opportunity to participate in an interdisciplinary problem of clinical interest and gain experience using procedures and instrumentation currently in use for diagnosis and treatment. It is hoped that the information obtained from these studies will add to our understanding of the mechanisms underlying host variability in the immune response.